The mission of our Perimenopause in Brain Aging and Alzheimer's Disease Program Project (P3) is to discover the biological transformations that occur in the brain during the perimenopausal transition which can result in phenotypes predicfive of risk for development of Alzheimer's pathology. We seek to identify the mechanisms by which these changes occur, and translate these discoveries to determine the opfimal timing and strategies for preventing conversion to the perimenopausal at-risk phenotype. To achieve our Perimenopausal Program Project mission, we will determine the perimenopausal phenotypes most at risk for developing biomarkers of Alzheimer's disease;delineate the mechanistic pathways involved in development of these phenotypes;and assess the impact of ovarian hormone and nutritional interventions on expression of Alzheimer's disease biomarkers. The mission of Analytic Core is to provide standardized steroid hormone regimens, sample archiving, processing and distribution, as well as analytic support across the Perimenopausal Program Project. To achieve this mission. Analytic Core will provide two levels of support. The first level of support entails Program-wide standardized steroid hormone regimens and sample management, which includes sample procuring, banking, distribufing, sample information recording through the central Integrafive Data Management System, and protein and RNA preparations (Specific Aim 1). The second level of support entails sample analysis and data interpretation on three major studies: (1) LC- MS/MS steroid hormone analysis (Specific Aim 2);(2) custom Taqman low-density array gene expression analysis (Specific Aim 3);and (3) bioinformafic gene funcfional analysis (Specific Aim 4). Analytic Core was an instrumental and essential resource for the currentiy ongoing Progesterone Program Project. Through the infrastructure and analytic methods it has developed. Analytic Core will continue to play a crucial role in achieving the Perimenopausal Program Project's missions and aims. RELEVANCE (See instructions): Women have a higher lifetime risk of developing Alzheimer's disease (AD) and represent -60% of the AD population. Discovery of at-risk phenotypes and the underiying mechanisms of phenotype development at perimenopausal transition could potentially lead to the eariy identification of those at greatest risk of developing AD and intervenfions to prevent the disease.